Part 1. Overview Information

This Funding Opportunity Announcement (FOA) is developed as a Common Fund initiative (https://commonfund.nih.gov/) through the Office of the NIH Director, Office of Strategic Coordination (https://dpcpsi.nih.gov). All NIH Institutes and Centers participate in Common Fund initiatives. This FOA will be administered by the National Institute of Neurological Disorders and Stroke (NINDS) on behalf of the NIH.

The purpose of this FOA is to support a Multisite Clinical Center to implement the enrollment and multimodal longitudinal assessment of a large cohort of patients that EITHER experienced an acute musculoskeletal trauma OR an acute peri-operative pain event to identify a biosignature for resilience to and/or the transition from acute to chronic pain.

Key Dates

Posted Date

August 29, 2019

Open Date (Earliest Submission Date)

October 25, 2019

Letter of Intent Due Date(s)

October 25, 2019

Application Due Date(s)

November 26, 2019.

All applications are due by 5:00 PM local time of applicant organization. All types of non-AIDS applications allowed for this funding opportunity announcement are due on the listed date(s).

Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.

Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions.

Applications that do not comply with these instructions may be delayed or not accepted for review.

There are several options available to submit your application through Grants.gov to NIH and
Department of Health and Human Services partners. You must use one of these submission
options to access the application forms for this opportunity.

Use the NIH ASSIST system to prepare, submit and track your application online.

Part 2. Full Text of Announcement

Section I. Funding Opportunity Description

BACKGROUND:

The United States faces a crisis due to the high prevalence of chronic pain and associated opioid use disorder and overdose deaths. More than 25 million adults in the U.S. report experiencing pain every day. A major challenge in pain care is the lack of evidence-based best practices to prevent chronic pain from occurring after an acute pain episode. For most people, acute pain resolves over time as the injury or trauma heals. In many people however, acute pain from injury, surgery, or disease processes persists well beyond the initial insult (sometimes throughout life) and is often intractable. Chronic pain persists beyond recovery due to changes in the peripheral and central nervous systems. However, the mechanisms driving acute pain transition to a chronic state are poorly understood.

The ability to predict which patients are more likely to be susceptible versus resilient to the development of chronic pain is a crucial step towards the development of personalized prevention strategies to transform acute pain treatment approaches and reduce or prevent chronic pain. Toward this end, the NIH Common Fund supported Acute to Chronic Pain Signatures (A2CPS) Program aims to identify biosignatures (a combination of several individual biomarkers) that predict susceptibility or resilience to the development of chronic pain after an acute pain event. Furthermore, if any of the predictive biomarkers identified through this program play a mechanistic role in the development of chronic pain, then the molecules, pathways, and/or brain circuits identified could serve as new potential therapeutic targets for reversing chronic pain or increasing patient resilience to chronic pain.

A2CPS is related to the multi-pronged HEAL (Helping to End Addiction Long-term) Initiative, an aggressive effort to speed scientific solutions to stem the national opioid public health crisis (https://www.nih.gov/research-training/medical-research-initiatives/heal-initiative). HEAL will build on extensive, well-established NIH research to address the opioid crisis and provide safer therapies for people with pain. Funding for A2CPS will be from the NIH Common Fund, which supports cross-cutting programs that are expected to have exceptionally high impact. All Common Fund initiatives invite investigators to develop bold, innovative, and often risky approaches to address problems that may seem intractable or to seize new opportunities that offer the potential for rapid progress.

Overall A2CPS Program Description: The A2CPS program will be funded as cooperative agreements through five linked FOAs. Awardees will work together as a consortium with strong communication and cooperation. The A2CPS program will support two longitudinal prospective studies (Multisite Clinical Centers (MCC) on large cohorts of patients who experience acute pain. Awards have been made in response to four A2CPS FOAs - Data Integration and Resource Center (DIRC), Omics Data Generation Centers (ODGCs), a Multisite Clinical Center (MCC): Acute Peri-Operative Pain, and a Clinical Coordination Center (CCC). Please see the A2CPS website for additional information concerning the Common Fund A2CPS Program. The goal of the A2CPS program is to identify candidate biomarkers and combine them into biosignatures predictive of the susceptibility or resilience to the development of chronic pain. The candidate biomarkers to be tested as primary outcomes in the two longitudinal prospective studies will be selected by a panel of external experts, consortium awardees, and NIH staff, who will consider the most promising biomarkers of transition or resilience to chronic pain based on current evidence. The size of each cohort is expected to be approximately 1800 patients, and the number of study biomarkers identified as primary study outcomes is expected to be approximately 40, based on a NIH power analysis calculation.

Overall, the A2CPS program will:

establish a Clinical Coordinating Center (CCC) (RFA-RM-18-035) to support study design, efficiency, and quality; develop protocols and contracts; establish a central IRB within the United States for the A2CPS program; train clinical staff in study procedures; and develop, coordinate, and monitor study implementation at the consortium’s clinical sites. The CCC will lead the development of the clinical protocols in the planning year.

support two Multisite Clinical Centers (MCCs) (RFA-RM-18-034 and RFA-RM-19-013), each of which will recruit one of the homogeneous pain cohorts at onset of an acute pain event; deliver, monitor, and record usual pain care including opioid and other analgesic use; assess patients for study-determined characteristics including detailed patient reported outcomes (historical data such as previous surgeries, trauma, substance abuse, concurrent pain conditions, depression, somatization tendencies, support system, etc.); perform brain imaging, sensory tests, and collect biospecimens at onset of acute pain and follow-up (time = 0, 3 months, and 6 months).

support one or more Omics Data Generation Centers (ODGCs) (RFA-RM-18-032) with expertise and resources to generate a diverse set of omics data from the biospecimens collected. Biospecimens will be analyzed extensively by the ODGCs using high-throughput technologies that allow rapid identification of many different biological molecules from large numbers of samples. Because the majority of the potential circulating/tissue biomarkers in the literature at this time are from 4 categories (proteomics, lipidomics, metabolomics, and extracellular RNA) it is expected the ODGCs will have expertise in these areas. Applicants to this component will be required to set aside 20% of their budget in order to add in any compelling additional omics assays identified during the planning year.

collect patient biospecimens sufficient for ODGC analysis. The ODGC will set aside 20% of the budget to have the flexibility to add assays as determined in the planning year. If additional funds become available, collection of additional biospecimens for future analysis by novel or dramatically improved assays may also be considered during the planning year. There will be a transparent and rigorous biospecimen reporting structure in place as well as a process by which PIs across the consortium can access biospecimens to perform tests. At the end of the study, we anticipate that unused biospecimens would be submitted to the NIH EPPIC Net Repository.?

establish a Data Integration Resource Center (DIRC) (RFA-RM-18-031) to receive data from the CCC, MCCs, and ODGCs for coordination, standardization, collection, integration, and statistical analysis of the clinical, imaging, and omics data. The DIRC will make the A2CPS data available to the scientific community using resources obtained through the NIH Data Commons (https://commonfund.nih.gov/commons) to ensure the data will be FAIR (Findable, Accessible, Interoperable, and Reusable) and accessible via cloud based data storage and computing. The DIRC also will develop a virtual biospecimen repository, build a publicly accessible database/website, coordinate logistics, such as organizing PI meetings, perform outreach activities, and submit the data to the appropriate data archives as needed.

be governed by a Steering Committee of A2CPS investigators and NIH staff that will oversee development of consensus policies, protocols, and procedures for consortium-wide activities such as clinical coordination, data collection, and resource sharing.

receive input on development and progress of the project from a panel of External Program Consultants (EPCs), a group of experts with broad, relevant expertise, who are independent of the awards.

Timeline: The first 6 months of an award made from this RFA (estimated to be summer 2020-January 2021) will be a planning period. Patient enrollment is estimated to begin in January 2021. The awardee for this project will join the A2CPS Steering Committee once the award is made.

Awards have been made in response to four FOAs in summer 2019. During the first (planning) year of the A2CPS program, the EPCs and Steering Committee will be established, the consortium will develop the clinical protocols, standard operating procedures, staff training plans, recruitment plans, electronic health record standardization, safety standards, and regulatory processes, identify biospecimen types and amounts to be collected, and develop biospecimen collection and storage protocols. The consortium will assess and refine the statistical analysis plan (including power analysis) for each cohort. At the kick-off meeting in September 2019, an expert panel, including consortium members, the EPCs, and outside experts will recommend approximately 40 evidence-based high value candidate biomarkers for primary study outcomes.

After satisfactory completion of the 6 month planning period, the awardee from this FOA will begin patient enrollment (January 2021). In January 2022 or at approximately 50% completion of 6 month phenotyping, a futility assessment will be performed to determine whether the rate of transition to chronic pain and patient retention is adequate to meet the assumptions of the power analysis. In the event of lower than expected transition or poor retention of patients, the A2CPS Steering Committee with the EPCs will make recommendations to NIH to either increase enrollment or terminate the study. NIH leadership will make the final determination. We expect enrollment to be complete by January 2023, and clinical assessments to be complete by July 2023. Data analysis and public archiving of the data for data mining efforts by the scientific community should be complete by August 2024.

FUNDING OPPORTUNITY:

The purpose of this FOA is to support one Multisite Clinical Center (MCC) to implement the enrollment and multimodal longitudinal assessment of a large cohort of EITHER an acute musculoskeletal trauma OR an acute peri-operative pain event patients to identify biosignatures for resilience to and/or the transition from acute to chronic pain. NIH staff may give priority to a musculoskeletal trauma grant vs. an acute peri-operative pain event grant. Applications will be reviewed for responsiveness to this FOA. A total knee arthroplasty (TKA) application will not be responsive to this FOA. No foreign applications or foreign components will be allowed. Applications deemed non-responsive to this FOA by NIH staff will be withdrawn without review. NIH staff do not anticipate that applications submitted to this FOA will be clinical trials given that there is no proposed intervention.

UM1 mechanism. Awards made under this FOA will be through the UM1 mechanism for Research Projects with Complex Structure. This mechanism is for cooperative agreements to support large-scale research activities with complicated structures that cannot be appropriately categorized into an available single component activity code. The components represent a variety of supporting functions and are not independent of one another. Substantial federal programmatic staff involvement is intended to assist investigators during performance of the research activities, as defined in the terms and conditions of the award. The UM1 is typically reserved for high-priority research areas that require a significant level of involvement from NIH staff (oversight, coordination, or facilitation).

Key activities of the MCC will be to:

communicate effectively with other consortium members (CCC, DIRC, ODGC, and the companion MCC) and NIH staff to achieve the overall goals of A2CPS. The MCC is expected to work as a consortium with the CCC, ODGCs, DIRC and companion MCC. Please see the other A2CPS FOAs for these components to gain a better understanding of the responsibilities for each component. These FOAs can be accessed via the Common Fund A2CPS website.

work with the consortium to assess and refine the power analysis for the consortium as a whole, to improve the likelihood of success.

recruit and enroll patients within the United States with selected acute pain event.

deliver, monitor, and record usual care, including pain care.

capture opioid use, including whether the patient is dependent on opioids at the 6-month assessment.

Applicants should plan to develop a study enrolling approximately 1800 patients over a two-year period from a SINGLE specific type of surgery OR a SINGLE specific type of musculoskeletal trauma (e.g. thoracotomy or other surgical procedure with expected 30% to 60% rate of transition from acute to chronic pain, or a bone fracture event with expected 30% to 60% rate of transition from acute to chronic pain) and retain these patients for assessments at time = 0, 3 months, and 6 months post-surgery. In other words, all 1800 patients in the study must have experienced the same surgery or musculoskeletal trauma.

Applicants should plan to provide justification for the selected surgical procedure OR musculoskeletal trauma with consideration of expected transition rate from acute to chronic pain based on the scientific literature and from their own preliminary data, if available.

Applicants should plan to provide a power analysis that will accommodate identification of multiple individual biomarkers to create predictive biosignatures.

Applicants should plan how the MCC will collaborate with the cross-consortium efforts.

Applicants should consider partnering with existing groups or leverage existing resources to achieve the goals of A2CPS. This could include partnering with the National Center for Advancing Translational Sciences' Trial Innovation Network (www.trialinnovationnetwork.org) and/or Clinical and Translational Science Award (CTSA) awardees.

Applicants should plan to propose and justify at least ten potential candidate biomarkers that they consider as the most compelling based on the scientific literature or from their own preliminary data.

Applicants should plan to include steps they will take to avoid unconscious experimenter bias with respect to diagnosis of transition chronic pain.

Applicants should plan for the PDs/PIs and essential team members to travel domestically for biannual meetings throughout the duration of the A2CPS program.

Informational Webinar. Prospective applicants are strongly encouraged to attend an informational webinar with NIH staff on September 19, 2019 from 11:00AM – 1:00PM EDT. Applicants also may contact NIH scientific staff and see the A2CPS FAQs (https://commonfund.nih.gov/pain/faq) for further information.

Section II. Award Information

Funding Instrument

Cooperative Agreement: A support mechanism used when there will be substantial Federal scientific or programmatic involvement. Substantial involvement means that, after award, NIH scientific or program staff will assist, guide, coordinate, or participate in project activities. See Section VI.2 for additional information about the substantial involvement for this FOA.

Application Types Allowed

New

The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types. Only those application types listed here are allowed for this FOA.

Clinical Trial?

Optional: Accepting applications that either propose or do not propose clinical trial(s)

The Office of Strategic Coordination (Common Fund) intends to commit $3.4 million in FY20 – this will include a 6 month preparation period as well as the first year of funds for recruitment, $2.5 million in FY21, and $700K in FY22.

Award Budget

Application budgets are not limited but need to reflect the actual needs of the proposed project.

Award Project Period

Projects cannot exceed three years including the FY20 planning period.

NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made from this FOA.

Section III. Eligibility Information

1. Eligible Applicants

Eligible Organizations

Higher Education Institutions

Public/State Controlled Institutions of Higher Education

Private Institutions of Higher Education

The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:

Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.

Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.

System for Award Management (SAM) – Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.

eRA Commons - Applicants must have an active DUNS number to register in eRA Commons. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration , but all registrations must be in place by time of submission. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.

Grants.gov – Applicants must have an active DUNS number and SAM registration in order to complete the Grants.gov registration.

Program Directors/Principal Investigators (PD(s)/PI(s))

All PD(s)/PI(s) must have an eRA Commons account. PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons. If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.

Eligible Individuals (Program Director/Principal Investigator)

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.

2. Cost Sharing

3. Additional Information on Eligibility

Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

The NIH will not accept duplicate or highly overlapping applications under review at the same time. This means that the NIH will not accept:

A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.

A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.

An application that has substantial overlap with another application pending appeal of initial peer review (see NOT-OD-11-101)

Section IV. Application and Submission Information

1. Requesting an Application Package

The application forms package specific to this opportunity must be accessed through ASSIST, Grants.gov Workspace or an institutional system-to-system solution. Links to apply using ASSIST or Grants.gov Workspace are available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

2. Content and Form of Application Submission

It is critical that applicants follow the instructions in the Research (R) Instructions in the SF424 (R&R) Application Guide except where instructed in this funding opportunity announcement to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

Letter of Intent

Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review.

By the date listed in Part 1. Overview Information, prospective applicants are asked to submit a letter of intent that includes the following information:

All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed

with the following exceptions:

The UM1 mechanism requires that the research strategy consist of separate components describing supporting functions that are interdependent. For this specific FOA, the research strategy should consist of the following sub-sections with the indicated page limits, all sections are required:

The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing an application to this FOA.

SF424(R&R) Cover

All instructions in the SF424 (R&R) Application Guide must be followed.

SF424(R&R) Project/Performance Site Locations

All instructions in the SF424 (R&R) Application Guide must be followed.

SF424(R&R) Other Project Information

All instructions in the SF424 (R&R) Application Guide must be followed.

SF424(R&R) Senior/Key Person Profile

All instructions in the SF424 (R&R) Application Guide must be followed.

R&R Budget

All instructions in the SF424 (R&R) Application Guide must be followed.

R&R Subaward Budget

All instructions in the SF424 (R&R) Application Guide must be followed.

PHS 398 Cover Page Supplement

All instructions in the SF424 (R&R) Application Guide must be followed.

PHS 398 Research Plan

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:

Specific Aims: The overall programmatic goal of the MCC is to implement the enrollment and multimodal longitudinal assessment of a large cohort of patients recovering from EITHER an acute musculoskeletal trauma OR an acute peri-operative pain event to identify biosignatures for resilience to and/or the transition from acute to chronic pain. Describe the goals of the MCC for the performance period of this project.

Research Strategy: The overall research strategy should be sure to address the following items:

Applicants must provide a timeline and detailed quantitative annual milestones throughout the funding period. If selected for funding, applicants will work with NIH staff to develop more granular quarterly milestones for each year of funding.

Applicants should provide a plan for enrolling approximately 1800 patients over a two-year period from a SINGLE specific type of surgery (e.g. thoracotomy or other surgical procedure with expected 30% to 60% rate of transition from acute to chronic pain) or a SINGLE specific type of musculoskeletal trauma (e.g., a bone fracture event with expected 30% to 60% rate of transition from acute to chronic pain) and retain these patients for assessments at time = 0, 3 months, and 6 months post-surgery. In other words, all patients in the study must have experienced the same surgery or the same musculoskeletal trauma. A description of the homogeneity of the patient cohort and evidence of the MCC’s ability to enroll this number of patients should be provided. We anticipate that enrollment will reflect the population of the US in terms of sex and ethnic diversity, take place across multiple sites, and use the central Institutional Review Board (IRB) set up by the CCC. Letters showing the willingness of the CCC or any other funded component of A2CPS to work with the applicant are NOT expected, since the A2CPS consortium will be required to work with the MCC funded from this RFA.

Applicants should provide justification for the selected surgical procedure or musculoskeletal trauma with consideration of expected transition rate from acute to chronic pain based on the scientific literature and from their own preliminary data, if available. The success of this project will depend in part on having a sufficiently high transition rate from acute to chronic pain.

Applicants should provide a power analysis that will accommodate identification of multiple individual biomarkers to create predictive biosignatures.

Applicants should describe how the MCC will collaborate with the cross-consortium efforts such as standardization of electronic health records, development of clinical protocols, safety standards, and biospecimen collection and storage protocols.

Applicants should consider partnering with existing groups or leverage existing resources to achieve the goals of A2CPS. This could include partnering with the National Center for Advancing Translational Sciences' Trial Innovation Network (www.trialinnovationnetwork.org) and/or Clinical and Translational Science Award (CTSA) awardees.

Although the biomarkers to be assessed will be selected by the consortium prior to any awards made from this FOA, applicants should propose at least ten potential biomarkers that they consider as the most compelling to study, based on the scientific literature or their own preliminary data, for EITHER a musculoskeletal trauma OR an acute peri-operative pain event. These candidate biomarkers could be in the areas of CNS imaging, patient reported outcomes, sensory testing, elements of the patient electronic health record, omics assays on biospecimens, or other well-justified areas. Examples of candidate biomarkers include patient reported psychosocial characteristics, targeted CNS changes, altered pain sensitivity and modulation, changes in the levels of a specific extracellular RNA species, protein, or metabolite, etc.

Applicants should describe steps they will take to avoid unconscious experimenter bias with respect to diagnosis of transition chronic pain.

Applicants should plan for the PDs/PIs and essential team members to travel domestically for biannual meetings throughout the duration of the A2CPS program.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide.

The following modifications also apply:

The following modifications also apply:

All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.

A primary goal of the A2CPS program is to facilitate discoveries by the broad scientific community. Restrictive sharing practices and licensing terms for A2CPS-generated data and resources could substantially diminish their value and public benefit. Accordingly, awardees are expected to manage data, resources, protocols, and software in a way that achieves this goal.

Applicants are required to submit a Public Access and Data Sharing Plan that (1) describes their proposed process for making resulting publications and to the extent possible, the underlying primary data immediately and broadly available to the public; or (2) if applicable, provides a justification to NIH if such sharing is not possible. Underlying Primary Data should be made as widely and freely available as possible while safeguarding the privacy of participants, and protecting confidential and proprietary data. NIH understands the content of a Public Access and Data Sharing Plan will vary depending on certain factors including, for example, the size and complexity of the dataset. However, the Public Access and Data Sharing Plan should, at a minimum, address the following general elements:

Electronic copies of Publications will be deposited in PubMed Central with proper tagging of metadata to ensure online discoverability and accessibility within four weeks of acceptance by a journal.

Publications will be Published under the Creative Commons Attribution 4.0 Generic License (CC BY 4.0) or an equivalent license, or otherwise dedicated to the public domain (e.g., Creative Commons public domain tool, CC0).

Publications will be made publicly available immediately without any embargo period.

Underlying Primary Data for the Publications will be made broadly available through an appropriate data repository such as the HEAL central data repository.

To the extent feasible, Underlying Primary Data will be shared simultaneously with the Publication and made immediately accessible through release under the Creative Commons Attribution 4.0 Generic License (CC BY 4.0) or an equivalent license, or otherwise dedicated to the public domain (e.g., Creative Commons public domain tool, CC0).

To meet program goals under this initiative, NIH requires broad and responsible sharing of Underlying Primary Data from NIH-Supported HEAL Projects that protects and maintains the privacy and confidentiality of participant data. If the research involves human subjects, as defined by 45 C.F.R. 465, the Public Access and Data Sharing Plan should discuss how the privacy rights of participants and confidentiality of their data will be protected and maintained in accordance with 45 C.F.R. 46 and other applicable laws and regulations.The Applicant should discuss the potential risks to research participants posed by data sharing and steps taken to address those risks, including the following:

Underlying Primary Data should be de-identified according to the standards set forth in the HHS Regulations for the Protection of Human Subjects to ensure that the identities of research subjects cannot be readily ascertained with the data.6 Underlying Primary Data should also be stripped of identifiers according to the Health Insurance Portability and Accountability Act (HIPAA) Privacy Rule.7 Underlying Primary Data that are free of identifiers but contain sensitive information are immediately released with no fee for access but are deposited in controlled access repositories with similar policies to dbGaP (e.g., the controlled access repository should have an independent data access committee and no financial incentives for limiting access to datasets).

Before submitting Underlying Primary Data, awardees through their Institutional Review Boards (IRBs)8, privacy boards9, or equivalent bodies10, will assess the informed consent materials to determine whether the Underlying Primary Data may be shared as contemplated in this Policy.

To meet program goals under this initiative NIH requires broad sharing of Underlying Primary Data from NIH-Supported HEAL Projects but is responsive to concerns with protecting confidential and proprietary data, ?and consistent with other applicable laws and regulations. The Public Access and Data Sharing Plan should describe any anticipated confidentiality concerns and how they will be addressed in accordance with the requirements of the Policy and meeting the programs goals of this initiative. For example, the data will be shared under licenses that retain intellectual property for commercialization but also have features that promote broad and immediate access (e.g., no embargo and no fee for access).

Applicants should indicate their willingness to abide by all data deposition, quality control metrics, standardization, metadata requirements, data and software release, and public copyright license policies developed by the A2CPS Steering Committee and approved by NIH staff, as well as NIH’s HEAL data sharing agreements for HEAL related projects. Sharing practices that hinder, prevent or block access to or use of A2CPS program data, tools, and resources for research purposes will not be considered acceptable. The development of policies, methods, and standards for such sharing is critically important. The NIH expects that the awardees, through the A2CPS Program Steering Committee, will develop such policies, methods, and standards in concert with the NIH. These policies, methods, and standards must remain consistent with NIH-wide policies on data and resource sharing.

Data deposition within A2CPS. Consistent with achieving the goals of this program, the NIH expects that information such as collected data (e.g. clinical measures, brain images, patient reported outcomes, sensory testing, metabolomics, lipidomics, proteomics, etc.), technical protocols, and any other data or metadata collected under this FOA will be deposited in the DIRC.

Data will be made available through the A2CPS portal as appropriate via the DIRC. The A2CPS portal will serve as the central access point for information regarding data, critical tools, protocols, and reagents developed by the A2CPS program. The A2CPS consortium will make the A2CPS data available to the scientific community using resources obtained through the NIH Data Commons (https://commonfund.nih.gov/commons) to ensure the data will be FAIR (Findable, Accessible, Interoperable, and Reusable) and accessible via cloud based data storage and computing.

A2CPS data will also be deposited by the DIRC (or possibly other A2CPS grantees) in appropriate public or controlled-access data repositories. Applicants should identify such repositories and describe plans for deposition. For datatypes that lack suitable public repositories, applicants should indicate their willingness to identify an appropriate alternative solution consistent with achieving the goals of the program.

Genomic Data Sharing Plan: If applicants propose to generate genomic data, they must indicate their willingness to abide by the NIH Genomic Data Sharing Policy (https://gds.nih.gov/) and should indicate their agreement to it in the data sharing plan.

Specific Plan for Protocol and Reagent Sharing. As one of the primary goals of this program is to advance research through development, establishment, broad dissemination and use of community resources across the research community, NIH intends that protocols and reagents generated by the A2CPS program be broadly available and distributed at minimal cost, and without undue intellectual property constraints, so that they can be as widely used as possible for research purposes by the larger scientific community. For all applications and where otherwise applicable, the applicant should discuss plans for sharing and distribution of non-data resources that will be generated by the proposed project. Applicants are encouraged to use Research Resource Identifiers (RRIDs).

The DIRC will work with all A2CPS program investigators to collect, curate, and disseminate information regarding reagents being developed by the program and to disseminate this information through the A2CPS Portal and other sources as appropriate and consistent with achieving the goals of the program.

Specific Plan for Sharing Software: A software dissemination plan, with appropriate timelines, is expected in applications proposing software development. There is no prescribed single license for software produced in this project. However, reviewers will be asked to evaluate the software sharing and dissemination plan based on its effectiveness. A dissemination plan guided by the following principles is thought to be the most effective:

The software should be freely available to biomedical researchers and educators in the non-profit sector, such as institutions of education, research institutions, and government laboratories.

The terms should also permit the dissemination and commercialization of enhanced or customized versions of the software, or incorporation of the software or pieces of it into other software packages.

To preserve utility to the community, the software should be transferable such that another individual or team can continue development in the event that the original investigators are unwilling or unable to do so.

The terms of software availability should include the ability of researchers outside the project and its collaborating projects to modify the source code and to share modifications with other colleagues. An applicant should take responsibility for creating the original and subsequent "official" versions of a piece of software.

Applicants are asked to propose a plan to manage and disseminate the improvements or customizations of their tools and resources by others. This proposal may include a plan to incorporate the enhancements into the "official" core software, may involve the creation of an infrastructure for plug-ins, or may describe some other solution. Any software dissemination plans represent a commitment by the institution (and its subcontractors as applicable) to support and abide by the plan

The A2CPS program aims to maximize the benefits of sharing, while protecting the intellectual property of the data generators. Prepublication sharing of data within the consortium will allow collaboration across initiatives and further the progress of the A2CPS program towards its goals and objectives. Therefore, the A2CPS program requires that data, metadata, and resources generated from A2CPS funding be made available to other A2CPS members immediately upon being considered “shareable”. When A2CPS-generated material under embargo is shared within the A2CPS program, it will be considered confidential with the understanding that the information will not be used or disclosed by A2CPS members unless explicitly agreed upon by the originator of the data under mutually acceptable terms. That is, consortium members may not publish using material generated by other consortium members without a collaboration or other agreement, or until the material in question has been made available to the public. A2CPS investigators accessing embargoed material only available to members of the A2CPS must sign a non-disclosure form agreeing to these terms.

Prior to funding, NIH Program Staff may negotiate modifications to the Sharing Plan with the applicant.

Appendix:

Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

PHS Human Subjects and Clinical Trials Information

When involving human subjects research, clinical research, and/or NIH-defined clinical trials (and when applicable, clinical trials research experience) follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

If you answered “Yes” to the question “Are Human Subjects Involved?” on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or Delayed Onset Study record.

Study Record: PHS Human Subjects and Clinical Trials Information

All instructions in the SF424 (R&R) Application Guide must be followed.

Delayed Onset Study

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).All instructions in the SF424 (R&R) Application Guide must be followed.

PHS Assignment Request Form

All instructions in the SF424 (R&R) Application Guide must be followed.

3. Unique Entity Identifier and System for Award Management (SAM)

See Part 1. Section III.1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and Grants.gov

4. Submission Dates and Times

Part I. Overview Information contains information about Key Dates and times. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission. When a submission date falls on a weekend or Federal holiday , the application deadline is automatically extended to the next business day.

Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies). Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date and time. If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH Policy on Late Application Submission.

Applicants are responsible for viewing their application before the due date in the eRA Commons to ensure accurate and successful submission.

Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide.

The requests by NIH intramural scientists will be limited to the incremental costs required for participation. As such, these requests will not include any salary and related fringe benefits for career, career conditional or other Federal employees (civilian or uniformed service) with permanent appointments under existing position ceilings or any costs related to administrative or facilities support (equivalent to Facilities and Administrative or F&A costs). These costs may include salary for staff to be specifically hired under a temporary appointment for the project, consultant costs, equipment, supplies, travel, and other items typically listed under Other Expenses. Applicants should indicate the number of person-months devoted to the project, even if no funds are requested for salary and fringe benefits.

If selected, appropriate funding will be provided by the Common Fund through the NIH Intramural Program. NIH intramural scientists will participate in this program as PD/PIs in accord with the Terms and Conditions provided in this FOA. Intellectual property will be managed in accord with established policy of the NIH in compliance with Executive Order 10096, as amended, 45 CFR Part 7; patent rights for inventions developed in NIH facilities are NIH property unless NIH waives its rights.

Should an extramural application include the collaboration with an intramural scientist, no funds for the support of the intramural scientist may be requested in the application. The intramural scientist may submit a separate request for intramural funding as described above.

7. Other Submission Requirements and Information

Applications must be submitted electronically following the instructions described in the SF424 (R&R) Application Guide. Paper applications will not be accepted.

For assistance with your electronic application or for more information on the electronic submission process, visit How to Apply – Application Guide. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Dealing with System Issues guidance. For assistance with application submission, contact the Application Submission Contacts in Section VII.

Important reminders:

All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF424(R&R) Application Package. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH. See Section III of this FOA for information on registration requirements.

The applicant organization must ensure that the DUNS number it provides on the application is the same number used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the SF424 (R&R) Application Guide.

Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review and responsiveness by components of participating organizations, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.

Post Submission Materials

Applicants are required to follow the instructions for post-submission materials, as described in the policy. Any instructions provided here are in addition to the instructions in the policy.

Section V. Application Review Information

1. Criteria

Only the review criteria described below will be considered in the review process. Applications submitted to the NIH in support of the NIH mission are evaluated for scientific and technical merit through the NIH peer review system.

In addition, for applications involving clinical trials:

A proposed Clinical Trial application may include study design, methods, and intervention that are not by themselves innovative but address important questions or unmet needs. Additionally, the results of the clinical trial may indicate that further clinical development of the intervention is unwarranted or lead to new avenues of scientific investigation.

Overall Impact

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the project proposed).

Scored Review Criteria

Reviewers will consider each of the review criteria below in the determination of scientific merit, and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field.

Significance

Does the project address an important problem or a critical barrier to progress in the field? Is the prior research that serves as the key support for the proposed project rigorous? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?

Will the proposed study transform our ability to predict the resilience to and/or transition from acute to chronic pain? Will the proposed study provide a foundation for further exploration of predictive biomarkers in other acute pain states or biomarkers indicative of chronic pain conditions? Will the study inform the design of future human studies for discovery of biomarkers? Will the study advance the science of clinical pain research?

In addition, for applications involving clinical trials

Are the scientific rationale and need for a clinical trial to test the proposed hypothesis or intervention well supported by preliminary data, clinical and/or preclinical studies, or information in the literature or knowledge of biological mechanisms? For trials focusing on clinical or public health endpoints, is this clinical trial necessary for testing the safety, efficacy or effectiveness of an intervention that could lead to a change in clinical practice, community behaviors or health care policy? For trials focusing on mechanistic, behavioral, physiological, biochemical, or other biomedical endpoints, is this trial needed to advance scientific understanding?

Investigator(s)

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or those in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?

Are key personnel well suited to their roles in the MCC? Have they demonstrated experience and accomplishments in managing clinical research? Has at least one member of the investigative team led a large complex clinical project? Does the team have expertise in the assessment of the patients in areas such as patient reported outcomes, sensory testing, CNS imaging, and biospecimen collection and storage? Does the team have expertise in the extraction of meaningful data and harmonization of electronic health records?

In addition, for applications involving clinical trials

With regard to the proposed leadership for the project, do the PD/PI(s) and key personnel have the expertise, experience, and ability to organize, manage and implement the proposed clinical trial and meet milestones and timelines? Do they have appropriate expertise in study coordination, data management and statistics? For a multicenter trial, is the organizational structure appropriate and does the application identify a core of potential center investigators and staffing for a coordinating center?

Innovation

Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?

In addition, for applications involving clinical trials
Does the design/research plan include innovative elements, as appropriate, that enhance its sensitivity, potential for information or potential to advance scientific knowledge or clinical practice?

Approach

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Have the investigators included plans to address weaknesses in the rigor of prior research that serves as the key support for the proposed project ? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed? Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects?

Have the investigators included plans to address weaknesses in the rigor of prior research that serves as the key support for the proposed project? Have the investigators included plans to address weaknesses in the rigor of prior research that serves as the key support for the proposed project?

In addition, for applications involving clinical trials

For all CT FOAs, add the following questions, after the standard questions for the Approach review criterion.

Does the application adequately address the following, if applicable

Study Design

Is the study design justified and appropriate to address primary and secondary outcome variable(s)/endpoints that will be clear, informative and relevant to the hypothesis being tested? Is the scientific rationale/premise of the study based on previously well-designed preclinical and/or clinical research? Given the methods used to assign participants and deliver interventions, is the study design adequately powered to answer the research question(s), test the proposed hypothesis/hypotheses, and provide interpretable results? Is the trial appropriately designed to conduct the research efficiently? Are the study populations (size, gender, age, demographic group), proposed intervention arms/dose, and duration of the trial, appropriate and well justified?

Are potential ethical issues adequately addressed? Is the process for obtaining informed consent or assent appropriate? Is the eligible population available? Are the plans for recruitment outreach, enrollment, retention, handling dropouts, missed visits, and losses to follow-up appropriate to ensure robust data collection? Are the planned recruitment timelines feasible and is the plan to monitor accrual adequate? Has the need for randomization (or not), masking (if appropriate), controls, and inclusion/exclusion criteria been addressed? Are differences addressed, if applicable, in the intervention effect due to sex/gender and race/ethnicity?

Are the plans to standardize, assure quality of, and monitor adherence to, the trial protocol and data collection or distribution guidelines appropriate? Is there a plan to obtain required study agent(s)? Does the application propose to use existing available resources, as applicable?

Data Management and Statistical Analysis

Are planned analyses and statistical approach appropriate for the proposed study design and methods used to assign participants and deliver interventions? Are the procedures for data management and quality control of data adequate at clinical site(s) or at center laboratories, as applicable? Have the methods for standardization of procedures for data management to assess the effect of the intervention and quality control been addressed? Is there a plan to complete data analysis within the proposed period of the award?

If the project involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of individuals of all ages (including children and older adults), justified in terms of the scientific goals and research strategy proposed?

Environment

Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?

Will the environment of the clinical sites enable the enrollment of the required number of patients? Do the clinical sites have the facilities and resources to perform the surgical procedure or treat the musculoskeletal trauma proposed and provide appropriate pain care? Will the facilities and staffing at the clinical sites enable assessment of the patients in areas such as patient reported outcomes, sensory testing, CNS imaging, and biospecimen collection and storage? Is the infrastructure to collaborate and communicate across the multiple sites within the MCC adequate and appropriate? Are resources available within the scientific environment to support electronic information handling? Will the Center benefit from unique features of the institutional environment, infrastructure, or personnel?

In addition, for applications involving clinical trials

If proposed, are the administrative, data coordinating, enrollment and laboratory/testing centers, appropriate for the trial proposed?

Does the application adequately address the capability and ability to conduct the trial at the proposed site(s) or centers? Are the plans to add or drop enrollment centers, as needed, appropriate?

If international site(s) is/are proposed, does the application adequately address the complexity of executing the clinical trial?

If multi-sites/centers, is there evidence of the ability of the individual site or center to: (1) enroll the proposed numbers; (2) adhere to the protocol; (3) collect and transmit data in an accurate and timely fashion; and, (4) operate within the proposed organizational structure?

Additional Review Criteria

As applicable for the project proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact score, but will not give separate scores for these items.

Study Timeline

Specific to applications involving clinical trials

Is the study timeline described in detail, taking into account start-up activities, the anticipated rate of enrollment, and planned follow-up assessment? Is the projected timeline feasible and well justified? Does the project incorporate efficiencies and utilize existing resources (e.g., CTSAs, practice-based research networks, electronic medical records, administrative database, or patient registries) to increase the efficiency of participant enrollment and data collection, as appropriate? Are potential challenges and corresponding solutions discussed (e.g., strategies that can be implemented in the event of enrollment shortfalls)?

Protections for Human Subjects

For research that involves human subjects but does not involve one of the categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.

For research that involves human subjects and meets the criteria for one or more of the categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.

Inclusion of Women, Minorities, and Individuals Across the Lifespan

When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of individuals of all ages (including children and older adults) to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.

Vertebrate Animals

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following criteria: (1) description of proposed procedures involving animals, including species, strains, ages, sex, and total number to be used; (2) justifications for the use of animals versus alternative models and for the appropriateness of the species proposed; (3) interventions to minimize discomfort, distress, pain and injury; and (4) justification for euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals. Reviewers will assess the use of chimpanzees as they would any other application proposing the use of vertebrate animals. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

Biohazards

Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.

Resubmissions

Not applicable

Renewals

Not applicable

Revisions

Not applicable

Additional Review Considerations

As applicable for the project proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact score.

Applications from Foreign Organizations

Not Applicable

Select Agent Research

Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).

For projects involving key biological and/or chemical resources, reviewers will comment on the brief plans proposed for identifying and ensuring the validity of those resources.

Budget and Period of Support

Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.

2. Review and Selection Process

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by CSR, in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.

As part of the scientific peer review, all applications:

May undergo a selection process in which only those applications deemed to have the highest scientific and technical merit (generally the top half of applications under review) will be discussed and assigned an overall impact score.

Will receive a written critique.

Appeals of initial peer review will not be accepted for applications submitted in response to this FOA.

Applications will be assigned to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the appropriate national Advisory Council or Board. The following will be considered in making funding decisions:

Scientific and technical merit of the proposed project as determined by scientific peer review.

Availability of funds.

Relevance of the proposed project to program priorities.

3. Anticipated Announcement and Award Dates

After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons. Refer to Part 1 for dates for peer review, advisory council review, and earliest start date.

Section VI. Award Administration Information

1. Award Notices

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement.

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization for successful applications. The NoA signed by the grants management officer is the authorizing document and will be sent via email to the grantee’s business official.

Awardees must comply with any funding restrictions described in Section IV.5. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.

Any application awarded in response to this FOA will be subject to terms and conditions found on the Award Conditions and Information for NIH Grants website. This includes any recent legislation and policy applicable to awards that is highlighted on this website.

Individual awards are based on the application submitted to, and as approved by, the NIH and are subject to the IC-specific terms and conditions identified in the NoA.

ClinicalTrials.gov: If an award provides for one or more clinical trials. By law (Title VIII, Section 801 of Public Law 110-85), the "responsible party" must register and submit results information for certain “applicable clinical trials” on the ClinicalTrials.gov Protocol Registration and Results System Information Website (https://register.clinicaltrials.gov). NIH expects registration and results reporting of all trials whether required under the law or not. For more information, see https://grants.nih.gov/policy/clinical-trials/reporting/index.htm

Institutional Review Board or Independent Ethics Committee Approval: Grantee institutions must ensure that all protocols are reviewed by their IRB or IEC. To help ensure the safety of participants enrolled in NIH-funded studies, the awardee must provide NIH copies of documents related to all major changes in the status of ongoing protocols. Data and Safety

Monitoring Requirements: The NIH policy for data and safety monitoring requires oversight and monitoring of all NIH-conducted or -supported human biomedical and behavioral intervention studies (clinical trials) to ensure the safety of participants and the validity and integrity of the data. Further information concerning these requirements is found at http://grants.nih.gov/grants/policy/hs/data_safety.htm and in the application instructions (SF424 (R&R) and PHS 398).

Investigational New Drug or Investigational Device Exemption Requirements: Consistent with federal regulations, clinical research projects involving the use of investigational therapeutics, vaccines, or other medical interventions (including licensed products and devices for a purpose other than that for which they were licensed) in humans under a research protocol must be performed under a Food and Drug Administration (FDA) investigational new drug (IND) or investigational device exemption (IDE).

Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights law. This means that recipients of HHS funds must ensure equal access to their programs without regard to a person’s race, color, national origin, disability, age and, in some circumstances, sex and religion. This includes ensuring your programs are accessible to persons with limited English proficiency. HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator’s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research.

In accordance with the statutory provisions contained in Section 872 of the Duncan Hunter National Defense Authorization Act of Fiscal Year 2009 (Public Law 110-417), NIH awards will be subject to the Federal Awardee Performance and Integrity Information System (FAPIIS) requirements. FAPIIS requires Federal award making officials to review and consider information about an applicant in the designated integrity and performance system (currently FAPIIS) prior to making an award. An applicant, at its option, may review information in the designated integrity and performance systems accessible through FAPIIS and comment on any information about itself that a Federal agency previously entered and is currently in FAPIIS. The Federal awarding agency will consider any comments by the applicant, in addition to other information in FAPIIS, in making a judgement about the applicant’s integrity, business ethics, and record of performance under Federal awards when completing the review of risk posed by applicants as described in 45 CFR Part 75.205 “Federal awarding agency review of risk posed by applicants.” This provision will apply to all NIH grants and cooperative agreements except fellowships.

The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 45 CFR Part 75, and other HHS, PHS, and NIH grant administration policies.

The administrative and funding instrument used for the A2CPS program will be the cooperative agreement, an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the awardees is anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the award recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the awardees for the project as a whole, although specific tasks and activities may be shared among the awardees and the NIH as defined below. Awardee will retain custody of and have primary rights to the data and software developed under this award, subject to Government rights of access consistent with current DHHS, PHS, and NIH policies.

Participating in group activities, including a Consortium-wide A2CPS Program Steering Committee and subcommittees as needed.

The A2CPS Consortium will meet at least twice a year throughout the duration of the A2CPS program, and the A2CPS Program Steering Committee will recommend the frequency of other in-person and teleconference meetings as needed.

Providing reports and data in a timely fashion as agreed upon by the A2CPS Program Steering Committee.

Submitting all data as soon as they are collected to the A2CPS DIRC for quality control.

Preparing abstracts, presentations and publications and collaborating Consortium-wide in making the public and professionals aware of the program.

Assessing and disseminating data, protocols, and methods developed for or derived from the A2CPS program within and outside the Consortium.

Adhering to policies regarding data sharing and publication established by the A2CPS Program Steering Committee and the NIH/NIH HEAL Initiative.

Abiding by common definitions, protocols, and procedures, as chosen by majority vote of the A2CPS Program Steering Committee.

Submitting periodic progress reports in a standard format, as agreed upon by the A2CPS Program Steering Committee and NIH A2CPS Working Group.

Attending and participating in A2CPS Program Steering Committee meetings and accepting and implementing decisions by the NIH A2CPS Working Group, as appropriate.

NIH staff will have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:

The NIH A2CPS Working Group consists of NIH programmatic staff from multiple Institutes and Centers of the NIH as well as the Office of the Director.

The NIH Project Scientist(s) will have substantial scientific and programmatic involvement during the conduct of this activity through technical assistance, advice, and coordination. However, the role of NIH staff will be to facilitate and not to direct the activities. The Project Scientist(s) will participate as members of the A2CPS Program Steering Committee and, the Project Scientists together will have a single vote. The Project Scientist(s) will have the following substantial involvement:

Participating with the other A2CPS Program Steering Committee members in addressing issues that arise with A2CPS planning, operation, assessment, and data analysis. The Project Scientist(s) will assist and facilitate the group process and not direct it.

Serving as a liaison, helping to coordinate activities, including acting as a liaison to other NIH Institutes/Centers, and as an information resource for the awardees. The Project Scientist(s) will also help coordinate the efforts of the A2CPS Consortium with other groups conducting similar efforts.

Attending all A2CPS Program Steering Committee meetings as a voting member, assisting in developing standard operating procedures, and consistent policies for dealing with situations that require coordinated action. The Project Scientist(s) will be responsible for working with the grantees as needed to manage the logistic aspects of the A2CPS program.

Reporting periodically on A2CPS progress to the Common Fund A2CPS Working Group and through it to the NIH Common Fund.

Serving on subcommittees of the A2CPS Program Steering Committee as appropriate.

Assisting awardees in the development, if needed, of policies for dealing with situations that require coordinated action.

Providing advice in the management and technical performance of the award.

Assisting in promoting the availability of the data and related resources developed in the course of this program to the scientific community at large.

Participating in data analyses, interpretations, and where warranted, co-authorship of the publication of results of studies conducted through the program.

Other NIH A2CPS Working Group staff may assist the awardee as designated by the Program Official.

Additionally, an agency Program Official or IC Program Director will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice. The assigned Program Official may also serve as an NIH Working Group Project Scientist(s) to assist the awardee. Prior to funding an application, the Program Official will contact the applicant to discuss the proposed milestones and any changes suggested by NIH staff or the NIH review panel. The Program Official and Project Scientist will negotiate with the applicant and agree on a final set of approved milestones which will be specified in the Notice of Award. The NIH Program Official, in consultation with the Project Scientist and NIH A2CPS Working Group, will determine if the awardee has met the milestones required for each year of funding.

NIH reserves the right to withhold funding or curtail an award in the event of:

Substantive changes in the project, or failure to make sufficient progress toward the work scope with which NIH concurred, or

Ethical or conflict of interest issues.

Areas of Joint Responsibility include:

Close interaction among the participating investigators will be required, as well as significant involvement from the NIH, to manage, assess, and disseminate the A2CPS program. The awardees and the Project Scientist(s) will meet in person with the A2CPS Program Steering Committee twice a year throughout the duration of the A2CPS programs, and on conference calls as needed to share information on methodologies, analytical tools, and preliminary results. PDs/PIs, key co-investigators and pre- and post-doctoral trainees, especially those who are members of under-represented minority groups or those from different but related disciplines, are eligible to attend these meetings.

The A2CPS Program Steering Committee will serve as the main scientific body of the program. The A2CPS Program Steering Committee will be responsible for coordinating the activities being conducted by the program and is the committee through which the NIH A2CPS Working Group formally interacts with the A2CPS investigators. The A2CPS Program Steering Committee membership will include PD(s)/PI(s) of each A2CPS award, other staff as needed (ex-officio) and the NIH Project Scientist(s). The A2CPS Program Steering Committee may add additional members, and other government staff may attend the A2CPS Program Steering Committee meetings as desired. Each project will have one vote and the NIH Program Scientist(s) together will have one vote.

The A2CPS Program Steering Committee may establish subcommittees as needed to address particular issues, which will include representatives from the program and the NIH and possibly other experts. The A2CPS Program Steering Committee will have the overall responsibility of assessing and prioritizing the progress of the various subcommittees.

The A2CPS awardee agrees to work collaboratively to:

Provide for secure, accurate and timely data submission.

Participate in presenting and publishing new processes and substantive findings.

Assess and disseminate A2CPS data and resources

Participate in the governance of the A2CPS program as a member of the A2CPS Program Steering Committee.

Interact with other relevant NIH activities, as needed, to promote synergy and consistency among similar projects.

External Program Consultants (EPCs):

A group of EPCs will be responsible for reviewing and evaluating the progress of the entire A2CPS program. The EPCs, as appropriate and at the request of the NIH A2CPS Working Group, also will provide input to the NIH about the progress of the individual A2CPS projects in meeting their individual and Consortium goals and milestones. The EPCs will be comprised of 4-8 senior, non-federal experts who are not directly involved in the activities of the A2CPS program and who have relevant scientific expertise. NIH will appoint the EPCs and select one member as chair. The A2CPS POs, PSs, NIH A2CPS Working Group, and other NIH staff may attend the EPC meetings.

The EPCs will meet at least once a year, in conjunction with a meeting of the A2CPS Program Steering Committee in the DC Metro area, to allow the EPCs to interact directly with the awardees, and by phone or email, at other times as needed.

Annually, the EPCs will provide their individual assessments to the NIH of the progress of the A2CPS Consortium and, as necessary, will present recommendations regarding any changes to the A2CPS program. The assessments and recommendations will be provided, through the NIH A2CPS Working Group, to the Director of the Office of Strategic Coordination, NIH.

Dispute Resolution:

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened. The three members will be: a designee of the A2CPS Program Steering Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual awardee. This special dispute resolution procedure does not alter the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR Part 16.

3. Reporting

A final RPPR, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement.

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for awardees of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All awardees of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000. See the NIH Grants Policy Statement for additional information on this reporting requirement.

In accordance with the regulatory requirements provided at 45 CFR 75.113 and Appendix XII to 45 CFR Part 75, recipients that have currently active Federal grants, cooperative agreements, and procurement contracts from all Federal awarding agencies with a cumulative total value greater than $10,000,000 for any period of time during the period of performance of a Federal award, must report and maintain the currency of information reported in the System for Award Management (SAM) about civil, criminal, and administrative proceedings in connection with the award or performance of a Federal award that reached final disposition within the most recent five-year period. The recipient must also make semiannual disclosures regarding such proceedings. Proceedings information will be made publicly available in the designated integrity and performance system (currently FAPIIS). This is a statutory requirement under section 872 of Public Law 110-417, as amended (41 U.S.C. 2313). As required by section 3010 of Public Law 111-212, all information posted in the designated integrity and performance system on or after April 15, 2011, except past performance reviews required for Federal procurement contracts, will be publicly available. Full reporting requirements and procedures are found in Appendix XII to 45 CFR Part 75 – Award Term and Conditions for Recipient Integrity and Performance Matters.

Section VII. Agency Contacts

We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.

Application Submission Contacts

eRA Service Desk (Questions regarding ASSIST, eRA Commons, application errors and warnings, documenting system problems that threaten submission by the due date, and post-submission issues)